In 2020, colorectal cancer (CRC) had over 1.9 million new cases and around 0.9 million deaths, making it the third most common cancer and the second leading cause of cancer deaths globally. GNAS mutations have been found in several cancers, including colon cancer, particularly in codon 201, which activates cAMP signaling and may lead to metastasis. The study aimed to find the frequency of the GNAS c.602G > A (p.Arg201His) mutation in CRC and analyze the pathology of tumors with this mutation. We collected a total of 40 tissue samples. DNA was extracted and analyzed using the High-Resolution Melting method followed by sequencing. In this study, 40 CRC patients were examined, revealing GNAS heterozygous mutations in 14 cases. Among these, 6 were women and 8 were men. Most cases (9) were grade 1 tumors, with varying sizes: 3 patients had tumors larger than 5 cm, 6 had tumors between 3 and 5 cm, and 5 had tumors smaller than 3 cm. Lymphatic involvement was observed in 5 patients. This study found a significant link between tumor size and lymphatic involvement, vascular metastasis, and gender. This study found that the heterozygous GNAS c.602G > A (p.Arg201His) mutation was present in a significant number of patients with CRC. There was a notable association between tumor size and lymphatic involvement, tumor size and vascular metastasis, and tumor size and gender. These findings suggest that the mutation may contribute to tumor progression and aggressive behavior in CRC. Therefore, it is important to further investigate GNAS mutations, as they could serve as potential molecular markers for predicting disease progression and guiding therapeutic decisions in CRC patients.